Synthesis and Antimicrobial Activity of Some New Nitrogen Bridgehead Pyrido [ 1 , 2-b ] [ 1 , 2 , 4 ] triazepines Incorporating 6-Methylchromone Moiety

Some new nitrogen bridge-head pyrido[1,2-b][1,2,4]triazepines incorporating 6methylchromone moiety have been synthesized from the reaction of 1,6-diamino-4-(6methyl-4-oxo-4H-chromen-3-yl)-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile (4) with some α,γ-bifunctional electrophiles including 2-cyano-3,3-bis(methylthio)acrylonitrile, 2cyano-3,3-bis(methylthio)prop-2-enamide, 5-chloro-3-methyl-1-phenylpyrazole-4carboxaldehyde, 2-chloro-3-formylquinoline, p-methoxybenzylidene-malononitrile, ethyl 2cyano-3-(4-methoxyphenyl)prop-2-enoate, chromone-3-carbonitrile. Structures of the newly synthesized products have been deduced upon the help of elemental analysis and spectral data. The synthesized compounds were screened for their antimicrobial activity.


ANTIMICROBIAL ACTIVITY
The standardized disc agar diffusion method [30] was followed to determine the activity of the synthesized compounds against the sensitive organisms Staphylococcus aureus as Gram positive bacteria, Proteus vulgaris as Gram negative bacteria and Candida albicans as fungus starin.The antibiotic Doxymycin and Fluconazole were purchased from Egyptian markets and used in concentrations 100 µg mL -1 as references for antibacterial and antifungal activities.
The compounds were dissolved in DMSO which has no inhibition activity to get concentration of 100 µg mL -1 .The results depicted in Table 1 showed various activities against all species of microorganisms which suggest that the variations in the structures affect on the growth of the microorganisms.Thus, we can conclude from these results: 1) The prepared compounds showed a variable antimicrobial activity towards all species of bacteria and fungi (Table 1).They showed antifungal activity higher than antibacterial activity.
2) Compounds 18 showed a good antimicrobial activity.This high effect may attribute to the presence of two skeletons of chromone moieties beside the triazolopyridone moiety.

EXPERIMENTAL
Melting points were determined on a digital Stuart SMP3 apparatus.Infrared spectra were measured on Perkin-Elmer 293 spectrophotometer (cm -1 ), using KBr disks. 1 H NMR (300MHz) were measured on Mercury-300BB, using DMSO-d 6 as a solvent and TMS (δ) as the internal standard.Mass spectra were obtained using Jeol-AMS-AX-500 instrument mass spectrometer (70 eV).Elemental microanalyses were performed at microanalysis unit in National Research Center, Dokki, Giza, Egypt.

Scheme 6 .
Scheme 6.The proposed mechanism for the formation of pyridotriazepine 19.

to produce the target product 5. The IR spectrum of compound 5 showed absorption bands at
).The reaction may proceed via nucleophilic displacement of SCH 3 group by the more nucleophilic amino group (N-NH 2 ) with concomitant cycloaddition of the other amino group (C-NH 2 ) onto nitrile function

Table 1 .
The antimicrobial activity of the newly synthesized Compounds.